Potential of Pandan Root and Teak Leaf Extracts in Managing Maternal Hyperglycemia During Pregnancy: Comparative Efficacy and Mechanistic Insights

Abstract

Maternal hyperglycemia during pregnancy poses significant health risks to both mother and fetus. Although gestational diabetes mellitus (GDM) is mainly characterized by insulin resistance, severe hyperglycemia may also result from impaired pancreatic function. This study evaluates the therapeutic potential of pandan (Pandanus amaryllifolius) root and teak (Tectona grandis) leaf extracts in managing streptozotocin (STZ)-induced maternal hyperglycemia in pregnant rats, compared to metformin. Methods: Pregnant rats were administered STZ (60 mg/kg) on gestation day 5. Treatments with metformin (300 mg/kg), pandan extract (low, medium, high doses), and teak extract (low, medium, high doses) were given from gestation day 7 to 21. The key parameters included the maternal blood glucose, insulin levels, pancreatic morphology, fetal and placental outcomes, and gas chromatography/mass spectrometry (GC/MS) phytochemical profiling. GC/MS analysis identified 2,3-butanediol and propanoic acid derivatives as major compounds in pandan, while teak contained catavic acid and methyl copalate. The high-dose pandan extract significantly reduced the maternal blood glucose (p < 0.05), improved the insulin levels and pancreatic mass index, and increased the number of live fetuses, with effects comparable to metformin. The teak extract showed milder improvements. The pandan extract demonstrated dose-dependent antidiabetic potential in this STZ-induced model. Future studies should evaluate these effects in insulin-resistance-based GDM models.

Keywords: gestational diabetes mellitus; maternal hyperglycemia; pandan root extract; streptozotocin-induced diabetes; teak leaf extract.

Figure 1

Gas chromatography–mass spectrometry (GC/MS) chromatograms and corresponding identified compounds. (A) GC/MS chromatogram and compound identification for pandan (Pandanus amaryllifolius) root extract. Peaks correspond to identified compounds, with their retention times and peak areas listed in the accompanying table. The major identified compounds include 2,3-butanediol (retention time: 6.224 min, peak area: 38.04%) and propanoic acid, 3,3′-thiobis-, dodecyl ester (retention time: 53.013 min, peak area: 9.70%). (B) GC/MS chromatogram and compound identification for teak (Tectona grandis) leaf extract. Identified compounds include catavic acid (retention time: 30.194 min, peak area: 21.22%) and methyl copalate (retention time: 31.010 min, peak area: 14.14%). Peaks are numbered in correspondence with the table below each chromatogram. Labeled peaks indicate the identified compounds in each sample. The x-axis represents the retention time (minutes), and the y-axis represents the signal intensity.

Figure 2

Experimental design and treatment schedule for gestational hyperglycemia induction and intervention in pregnant rats. Pregnant rats were divided into experimental groups based on the treatments, including a non-diabetic control, diabetic control, metformin-treated, and various doses of pandan and teak extracts. Gestational hyperglycemia was induced using intraperitoneal injection of streptozotocin (STZ) at 60 mg/kg in citrate buffer on gestation day 5. Diabetic confirmation was conducted on gestation day 7, after which daily oral administration of the treatments (metformin, pandan extract, or teak extract) was initiated. The maternal body weight (BW), blood glucose levels, and food consumption were monitored at gestation days 0, 7, 14, and 21. On gestation day 21, the animals were sacrificed for the pregnancy outcome assessment, blood sample collection, and insulin level measurement.

Figure 3

Maternal blood glucose levels (mg/dL) during pregnancy in different experimental groups. The blood glucose levels were measured on gestation days 0, 7, 14, and 21 in pregnant rats assigned to different treatment groups: control (non-diabetic), streptozotocin (STZ)-induced hyperglycemic (untreated), metformin-treated, and varying doses of pandan and teak extracts. On gestation day 0, all the groups showed similar baseline blood glucose levels. By gestation day 7, STZ administration significantly increased the blood glucose levels in all the experimental groups compared to the control (p < 0.05). The blood glucose remained elevated in untreated hyperglycemic rats (STZ group), while metformin and high doses of pandan and teak extracts exhibited a trend of glucose reduction by gestation days 14 and 21. Groups labeled with different superscript letters denote statistically significant differences (p < 0.05; n = 5 per group). Data are expressed as the mean ± standard deviation (SD) and were analyzed using one-way ANOVA followed by Tukey’s post hoc test (p < 0.05).

Figure 4

Maternal body weight (g) during pregnancy in the different experimental groups. The maternal body weight was measured on gestation days 0, 7, 14, and 21 in pregnant rats assigned to the different treatment groups: control (non-diabetic), streptozotocin (STZ)-induced hyperglycemic (untreated), metformin-treated, and varying doses of pandan and teak extracts. On gestation days 0 and 7, the maternal body weights across all the groups remained similar and within the baseline range. By gestation day 14, STZ administration significantly decreased the maternal body weight in all the experimental groups compared to the control group (p < 0.05). High-dose pandan extract significantly increased the maternal body weight on gestation day 21 compared to the untreated hyperglycemic rats (STZ group, p < 0.05). Groups labeled with different superscript letters denote statistically significant differences at the same time point (p < 0.05; n = 5 per group). Data are expressed as the mean ± standard deviation (SD) and were analyzed using one-way ANOVA followed by Tukey’s post hoc test (p < 0.05).

Figure 5

Maternal insulin levels (pg/mL) at gestation day 21 in the different experimental groups. The insulin levels were measured in pregnant rats across the treatment groups: control (non-diabetic), streptozotocin (STZ)-induced hyperglycemic (untreated), metformin-treated, and varying doses of pandan and teak extracts. The control group exhibited significantly higher insulin levels compared to all the other groups (p < 0.05), while the STZ-induced hyperglycemic rats and treated groups showed lower insulin levels, with no significant differences among the treatments. Groups labeled with different superscript letters denote statistically significant differences (p < 0.05; n = 5 per group). Data are expressed as the mean ± standard deviation (SD) and were analyzed using one-way ANOVA followed by Tukey’s post hoc test (p < 0.05).

Figure 6

Pancreatic mass index and relative islet area quantification in the different experimental groups at gestation day 21. (A) Pancreatic mass index (%). The pancreatic mass index was calculated as the ratio of pancreatic weight to body weight in pregnant rats from the different treatment groups: control (non-diabetic), streptozotocin (STZ)-induced hyperglycemic (untreated), metformin-treated, and varying doses of pandan and teak extracts. The STZ group exhibited the lowest pancreatic mass index, whereas the medium-dose pandan group showed a significant increase compared to STZ (p < 0.05). (B) Relative islet area quantification (µm²). The pancreatic islet area was measured to assess the β-cell preservation among groups. The control group showed the largest islet area, while the STZ-induced hyperglycemic group exhibited a significant reduction. Treatment with metformin, medium-dose pandan, and high-dose teak extracts resulted in partial islet preservation compared to STZ (p < 0.05). Groups labeled with different superscript letters denote statistically significant differences (p < 0.05; n = 5 per group). Data are expressed as the mean ± standard deviation (SD) and were analyzed using one-way ANOVA followed by Tukey’s post hoc test (p < 0.05).

Figure 7

Histological analysis of pancreatic islets in the different experimental groups. Representative hematoxylin and eosin (H&E)-stained photomicrographs of pancreatic islets from pregnant rats at 400× magnification (scale bar: 20 μm). Pancreatic islets are outlined in black. (A) Control group: normal islet architecture with well-preserved β-cell distribution. (B) Streptozotocin (STZ)-induced hyperglycemic group: marked reduction in islet size and disrupted cellular arrangement. (C) Metformin-treated group: partial preservation of islet structure and increased β-cell density. (D–F) Pandan extract-treated groups: dose-dependent improvement in islet structure, with higher doses showing greater preservation. (G–I) Teak extract-treated groups: improved islet morphology in higher doses compared to STZ-induced hyperglycemia. The islet size and morphology were used as indicators of gestational hyperglycemia-associated pancreatic changes.

Figure 8

Pregnancy outcomes in different experimental groups at gestation day 21. (A) Number of live fetuses: the streptozotocin (STZ)-induced hyperglycemic group exhibited a lower number of live fetuses compared to the control and treatment groups. Treatment with pandan and teak extracts, particularly at medium and high doses, improved fetal survival (p < 0.05). (B) Number of dead fetuses: the STZ-induced hyperglycemic group showed a higher number of dead fetuses, though the variations among treatment groups were not statistically significant. (C) Number of resorptions: resorption rates were elevated in the STZ-induced group, while the pandan and teak extract treatments showed a trend of reduction. (D) Number of corpora lutea: no significant differences were observed among the groups, indicating consistent ovulation rates before pregnancy. (E) Number of implantation sites: the number of implantation sites remained relatively similar across the groups, suggesting that hyperglycemia mainly affected fetal development rather than implantation success. (F) Pre-implantation loss (%): increased pre-implantation loss was observed in the STZ-induced hyperglycemic group compared to the control and treated groups. (G) Post-implantation loss (%): the STZ-induced hyperglycemic group showed the highest post-implantation loss, while treatment with pandan and teak extracts appeared to mitigate this effect. Groups labeled with different superscript letters denote statistically significant differences (p < 0.05; n = 5 per group). Data are expressed as the mean ± standard deviation (SD) and were analyzed using one-way ANOVA followed by Tukey’s post hoc test (p < 0.05).

Figure 9

Fetal and placental outcomes in different experimental groups at gestation day 21. (A) Fetal weight (g): the streptozotocin (STZ)-induced hyperglycemic group exhibited significantly lower fetal weight compared to the control (p < 0.05). Treatment with metformin, pandan, and teak extracts increased the fetal weight, with the medium- and high-dose pandan groups showing the most improvement. (B) Placental weight (g): the STZ-induced group had significantly lower placental weight compared to the control (p < 0.05). Treatment with metformin and high-dose pandan resulted in improved placental weight, suggesting a protective effect. (C) Placental index (%): the placental index (placental weight relative to fetal weight) was significantly higher in the STZ-induced hyperglycemic group than in the control, indicating placental insufficiency. Treatment groups, particularly metformin and medium-dose pandan, showed a trend toward normalization. (D) Fetal blood glucose levels (mg/dL): the fetal blood glucose was significantly elevated in the STZ-induced hyperglycemic group compared to the control (p < 0.05). Treatment with metformin, medium-dose pandan, and high-dose teak reduced the fetal glucose levels, indicating potential glycemic control benefits. Groups labeled with different superscript letters denote statistically significant differences (p < 0.05; n = 5 per group). Data are expressed as the mean ± standard deviation (SD) and were analyzed using one-way ANOVA followed by Tukey’s post hoc test (p < 0.05).

Figure 10

The half-maximal inhibitory concentration (IC₅₀) values of the pandan and teak extracts. The pandan extract showed a clear dose-dependent effect, confirming its potential antidiabetic properties. The teak extract failed to produce a measurable IC₅₀, suggesting weak or variable bioactivity that may require further optimization or alternative extraction methods.